Preclinical prototype validation and characterization of a thermobrachytherapy system for interstitial hyperthermia and high-dose-rate brachytherapy

Background and purpose Integrating simultaneous interstitial hyperthermia in high-dose-rate brachytherapy treatments (HDR-BT) is expected to lead to enhanced therapeutic effect. However, there is currently no device available for such an integration. In this study, we presented and validated the thermobrachytherapy (TBT) preclinical prototype system that is able to seamlessly integrate into the HDR-BT workflow. Materials and methods The TBT system consisted of an advanced radiofrequency power delivery and control system, dual-function interstitial applicators, and integrated connection and impedance matching system. The efficiency and minimum heating ability of the system was calculated performing calorimetric experiments. The effective-heating-length and heating pattern was evaluated using single-applicator split phantom experiments. The heating independence between applicators, the ability of the system to adaptable and predictable temperature steering was evaluated using multi-applicator split phantom experiments. Results The system satisfied interstitial hyperthermia requirements. It demonstrated 50 % efficiency and ability to reach 6 °C temperature increase in 6 min. Effective-heating-length of the applicator was 43.7 mm, following the initial design. Heating pattern interference between applicators was lower than recommended. The system showed its ability to generate diverse heating patterns by adjusting the phase and amplitude settings of each electrode, aligning well with simulations (minimum agreement of 88 %). Conclusions The TBT preclinical prototype system complied with IHT requirements, and agreed well with design criteria and simulations, hence performing as expected. The preclinical prototype TBT system can now be scaled to an in-vivo validation prototype, including an adaptable impedance matching solution, appropriate number of channels, and ensuring biocompatibility and regulatory compliance.


RADIOFREQUENCY POWER DELIVERY AND CONTROL SYSTEM DESCRIPTION 12
The custom built power delivery and control system architecture can be seen in diagram of oscillator (Skyworks Solutions, USA), is given as input to the five integrated circuits, and the system clocks of four synthesizers 22 (secondary) are programmatically synchronized to the fifth one (primary).The latter is done by an automatic synchronization 23 method integrated in the AD9959 synthesizer, that which sends a synchronization pulse from the controller synthesizer (SYNC 24 OUT) to the worker synthesizers (SYNC IN). 25 The DDS system can produce 10 synchronous signals with a frequency of 27 MHz and a phase shift in the range of 0-360° with 26 a step size of 0.1°.The signal amplitude can be varied between -60 dBm and -7 dBm in steps of 27 1 dBm.The settings can be monitored and controlled manually or with a PC using a serial communication port.28 High Power Amplifiers

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The high-power amplification system consists of ten WSDU-1x2PM amplifiers (Becker Nachrichtentechnik, Germany) 30 controlled by a SR6-CU controller unit (Becker Nachrichtentechnik, Germany) (Fig. 1.c).The amplifier modules consist of a 2-1 way multicoupler with a variable output power of up to 5 W per channel.The modules have a typical variable gain ranging from 2 +19.25 dB to +51 dB at the frequency of 27 MHz, and a resolution of 0.25 dB.Furthermore, the modules have integrated forward 3 power sensors with a typical accuracy of 0.3 dB.The controller unit communicates with a PC using serial communication. 4 Power detection and control

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Whilst forward power sensors are integrated in the amplifier modules, reflected power sensors are not.Therefore, an external 6 power sensor is connected at the output of each amplifier, using a ZFBDC20-62HP-S+ 20 dB Bi-directional coupler (Minicircuits, 7 USA).The PWR-4GHS power sensor (Minicircuits, USA) can measure power on a wide range of power levels (1 μW to 0.1 W), 8 covering the whole range of possible power outputs and being able to measure reflected power levels down to -10 dBm (given the 9 -20 dB coupling).This gives the system the ability to evaluate the reflection coefficient even at low power outputs with a maximum 10 power measurement uncertainty of ±0.35 dB.11 For proper power leveling, a calibration of the power system is performed with all outputs connected to 50 Ω loads.With a 12 polynomial fit in the power range of operation, the desired forward power level can be matched instantly given that the input 13 frequency and amplitude remain stable.When a mismatch occurs, the power is adapted with a proportional-integral-derivative 14 controller (PID controller) to the desired effective output power.15

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is based on five AD9959 multichannel frequency synthesizer integrated circuits (Analog Devices, USA), each 18 mounted on its own circuit board and controlled through an ATMega2560 microcontroller (Fig. 1.c).Each AD9959 integrated 19 circuit can produce four digitally synthesized coherent output signals, with independent frequency, phase, and amplitude 20 modulation.To synchronize all five synthesizers, an external 125 MHz reference signal, generated by an Si514 programmable 21

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Fig. A.1.diagram of the power delivery and control system.